Molecular Inclusion Research Articles

Evaluation of molecular inclusion of azole antifungals by β-cyclodextrin using computational molecular approach

Fungal infection is an emerging global concern highlighting diseases like pneumonia, invasive candidiasis, chronic pulmonary aspergillosis, and meningitis. But major concern is development of antifungal drug resistance, necessitating novel pharmacological solutions. Azoles, particularly fluconazole and related compounds, are emphasized for their systemic efficacy via inhibition of CYP51, altering fungal cell membrane sterols. So, in this work we theoretically investigated the effect of complexation of azoles with β-cyclodextrin (β-CD), focusing on improving solubility and bioavailability. Using molecular docking, the interaction between azoles and β-CD is analyzed, predicting stability and binding energies. Docking studies elucidate specific binding modes and hydrogen bonding interactions, while PM3 calculations provide insights into electronic structures and properties such as HOMO–LUMO energy gaps, chemical potential, hardness, and electrophilicity. Our findings indicate that fluconazole-β-CD complexes, particularly FCZ-βCD2, exhibit stability and promising development potential due to low energy and favorable binding characteristics. The antifungal spectrum of all the inclusion complexes was predicted using the PASS web server which proved that that the complexes are more effective against fungal pathogens than bacterial pathogens. This preliminary theoretical study highlights β-CD’s potential as a carrier to enhance the therapeutic efficacy of antifungal drugs, addressing key challenges in treating fungal infections through improved solubility and bioavailability.

Curcumin- β-Cyclodextrin Molecular Inclusion Complex: A Water-Soluble Complex in Fast-dissolving Tablets for the Treatment ofNeurodegenerative Disorders.

Orally disintegrating tablets (ODTs) have become an excellent choice for delivering drugs as their palatability is greatly improved. In this work, β-cyclodextrin has been used to improve the solubility of curcumin by encapsulating it into the hydrophobic cavity for the treatment of neurodegenerative disorders. The current study aimed to present the design, formulation, and optimisation of fastdissolving oral tablets of curcumin- β-cyclodextrin molecular inclusion complex using a 32-factorial design. The drug-excipient compatibility was studied by FTIR spectroscopy. The inclusion complex of curcumin-β-cyclodextrin was prepared using solvent casting and confirmed using XRD studies. Powder blends were evaluated for flow properties. Tablets prepared by direct compression were evaluated for post-compression parameters. Further, the effect of formulation variables, such as sodium starch glycolate (X1) and Neusilin® ULF2 (X2), on various responses, including disintegration time and dissolution at 2 hours, was studied using statistical models. Post-compression parameters, i.e., hardness (4.4-5 kg/cm2), thickness (3.82-3.93 mm), weight variation (±7.5%), friability (< 1%), wetting time (51-85 seconds) and drug content (96.28- 99.32%) were all found to be within the permissible limits and the disintegration time of tablets with super-disintegrants ranged between 45-58 seconds. The in-vitro dissolution profile of tablets showed that higher SSG and Neuslin® ULF2 levels promoted drug release. For statistical analysis, the 2FI model was chosen. Optimised variables for formulation have been determined and validated with the experimental findings based on the significant desirability factor. The current study reveals the validated curcumin-β-cyclodextrin inclusion complex fastdissolving tablets with SSG and Neusilin® ULF2 to be an ideal choice for effectively treating neurodegenerative disorders.

Effect of screening with a pan-TRK immunohistochemistry-based algorithm on NTRK fusion detection rates.

e15135 Background: Rearrangements in the NTRK1, NTRK2, and NTRK3 genes are clinical actionable and predictive of response to TRK kinase inhibitors in solid tumors. Their detection in clinical practice is a priority, but their low prevalence (0.25-1%) poses a diagnostic challenge. In this study, we describe our immunohistochemical-based and cost-effective approach for NTRK rearrangements detection. Methods: We implemented a comprehensive NTRK testing approach at a reference center that combined clinical criteria (e.g., iodine therapy-resistant thyroid cancer); molecular biomarkers (e.g., non-small-cell lung carcinoma negative for driver alterations, colorectal carcinoma with deficient MMR and/or microsatellite instability); and histopathological criteria (identifying tumor subtypes associated with NTRK fusions, such as breast secretory carcinoma). Automated immunohistochemistry (Ventana BenchMark ULTRA IHC/ISH System) using the antibody pan-TRK (Ventana, EPR17341) was used as a screening tool. Positive results were confirmed through molecular techniques, including Next Generation Sequencing, NGS (Oncomine Focus Assay, Thermo Fisher, based on DNA and RNA) and/or FISH (NTRK3 break-apart probe, Zytovision). Results: We evaluated 172 patients (99 female/73 male), with a mean age of 52 years (SD 23.8). Eighteen (18) patients with neoplasms expressing TRK proteins were identified. Confirmatory studies using NGS identified fusions in 7 cases. In instances of poor RNA quality, FISH techniques (NTRK3) were employed, confirming the findings in an additional 3 patients. Overall prevalence of NTRK fusions was 5.8%. Histological types included the following tumor types: Thyroid carcinoma, 4 patients (one medullary and 3 papillary carcinomas, two of them in the pediatric population); soft tissue sarcomas, 3 patients (2 corresponding to infantile fibrosarcoma and a soft tissue provisional entity, "NTRK-rearranged spindle cell neoplasm”); secretory carcinoma of the breast, one patient; secretory carcinoma of the salivary gland, one patient; colorectal carcinoma, one patient, with a deficient MMR phenotype. NTRK3 gene fusions were found in 10 patients, (6 fusions with ETV6 detected by NGS and 3 detected by FISH), and NTRK1 fusion in 1 case (fusion with LMNA detected by NGS). The positive predictive value of pan-TRK immunohistochemistry as a screening tool was 0.55. Conclusions: In our experience, the comprehensive screening approach based on morphological and clinical/ molecular inclusion criteria, along with the use of immunohistochemical techniques (pan-TRK antibody), significantly enhances the detection rate of NTRK fusions (5.8% vs. 0.25-1%). Additionally, FISH provides a valuable tool in samples with poor RNA quality. This approach allows for a reduction in the impact of costly testing, such as NGS, on the healthcare system.

Integrated genomic and transcriptomic characterization of neuroendocrine carcinomas for improved treatment decision-making.

e15138 Background: Neuroendocrine carcinomas (NECs) are poorly characterized due to their innate heterogeneity, thus limiting treatment and clinical trial options for patients. Here, we used whole exome sequencing (WES) and RNA sequencing (RNA-seq) to explore the genetic and microenvironmental landscape of NECs in order to understand the unique features of different NEC types, with the aim of improving treatment modalities. Methods: We analyzed 51 NEC clinical samples morphologically verified by a pathologist: lung NEC (20 small cell NEC and 1 large cell NEC cases), gastroenteropancreatic NEC (GEP, 12 cases), cancer of unknown primary (7 cases), Merkel cell carcinoma (MCC, 5 cases), genitourinary tract NEC (3 cases), and breast NEC (3 cases). Findings on tumor mutational burden (TMB, mut/Mb), microsatellite instability (MSI), gene expression signatures, and tumor microenvironment (TME) profiling were reported. Small cell lung cancer (SCLC) subtyping was performed as reported by Gay et al. on the entire NEC cohort. Results: Half of the patients with lung NEC and 84% of those with extrapulmonary NEC satisfied the molecular inclusion criteria for clinical trials, with the most frequent criterion being KRAS G12X or G13X mutations. Among the extrapulmonary NEC samples, 13.7% were deemed eligible for targeted therapy, specifically for cases with BRAF V600E mutation and/or high TMB (&gt; 10 mut/Mb). We detected varying TMB and distinct gene expression features across the entire cohort. Specifically, we found 2 MCC cases to be Merkel cell polyomavirus-positive with low TMB and devoid of UV-associated mutations. One GEP-NEC case exhibited a high MSI (MSI-high) status. We detected 6 SCLC cases (3 non-smokers, 3 former smokers) with surprisingly low levels of tobacco-associated mutations (&lt;10% of all mutations). Two GEP-NEC cases had high levels of mutations associated with tobacco smoking. While TME profiling showed no significant difference in cell population makeup across all samples, transcriptional SCLC subtyping revealed significant differences among the cases. Inflammatory SCLC (SCLC-I) samples showed statistically significant enrichment of all subpopulations of the immune microenvironment (i.e., B cells, T cells, NK cells), supporting the use of immune checkpoint blockade for treatment. The POU2F3+ SCLC (SCLC-P) samples showed low expression of all neuroendocrine diagnostic markers (i.e., INSM1, NCAM1, SYP, CHGA). Conclusions: Given the heterogeneous molecular features across diverse NEC tumors, a uniform treatment strategy is unlikely to benefit all NEC patients. Hence, our ability to detect these unique molecular features is crucial for matching individual NEC patients with specific clinical trials and targeted therapies that may improve their outcomes. Thus, a concerted effort using in-depth genomic, transcriptomic, and TME profiling for NEC tumors is warranted.

Integrating depth-dependent protist dynamics and microbial interactions in spring succession of a freshwater reservoir

BackgroundProtists are essential contributors to eukaryotic diversity and exert profound influence on carbon fluxes and energy transfer in freshwaters. Despite their significance, there is a notable gap in research on protistan dynamics, particularly in the deeper strata of temperate lakes. This study aimed to address this gap by integrating protists into the well-described spring dynamics of Římov reservoir, Czech Republic. Over a 2-month period covering transition from mixing to established stratification, we collected water samples from three reservoir depths (0.5, 10 and 30 m) with a frequency of up to three times per week. Microbial eukaryotic and prokaryotic communities were analysed using SSU rRNA gene amplicon sequencing and dominant protistan groups were enumerated by Catalysed Reporter Deposition-Fluorescence in situ Hybridization (CARD-FISH). Additionally, we collected samples for water chemistry, phyto- and zooplankton composition analyses.ResultsFollowing the rapid changes in environmental and biotic parameters during spring, protistan and bacterial communities displayed swift transitions from a homogeneous community to distinct strata-specific communities. A prevalence of auto- and mixotrophic protists dominated by cryptophytes was associated with spring algal bloom-specialized bacteria in the epilimnion. In contrast, the meta- and hypolimnion showcased a development of a protist community dominated by putative parasitic Perkinsozoa, detritus or particle-associated ciliates, cercozoans, telonemids and excavate protists (Kinetoplastida), co-occurring with bacteria associated with lake snow.ConclusionsOur high-resolution sampling matching the typical doubling time of microbes along with the combined microscopic and molecular approach and inclusion of all main components of the microbial food web allowed us to unveil depth-specific populations’ successions and interactions in a deep lentic ecosystem.

Inclusion Complexes of Litsea cubeba (Lour.) Pers Essential Oil into β-Cyclodextrin: Preparation, Physicochemical Characterization, Cytotoxicity and Antifungal Activity.

The uses of natural compounds, such as essential oils (EOs), are limited due to their instability to light, oxygen and temperature, factors that affect their application. Therefore, improving stability becomes necessary. The objective of this study was to prepare inclusion complexes of Litsea cubeba essential oil (LCEO) with β-cyclodextrin (β-CD) using physical mixing (PM), kneading (KN) and co-precipitation (CP) methods and to evaluate the efficiency of the complexes and their physicochemical properties using ATR-FTIR, FT-Raman, DSC and TG. The study also assessed cytotoxicity against human colorectal and cervical cancer cells and antifungal activity against Aspergillus flavus and Fusarium verticillioides. The complexation efficiency results presented significant evidence of LCEO:β-CD inclusion complex formation, with KN (83%) and CP (73%) being the best methods used in this study. All tested LCEO:β-CD inclusion complexes exhibited toxicity to HT-29 cells. Although the cytotoxic effect was less pronounced in HeLa tumor cells, LCEO-KN was more active against Hela than non-tumor cells. LCEO-KN and LCEO-CP inclusion complexes were efficient against both toxigenic fungi, A. flavus and F. verticillioides. Therefore, the molecular inclusion of LCEO into β-CD was successful, as well as the preliminary biological results, evidencing that the β-CD inclusion process may be a viable alternative to facilitate and increase future applications of this EO as therapeutic medication, food additive and natural antifungal agent.

EXTRACTO ANTIOXIDANTE ENCAPSULADO POR ATOMIZACIÓN Y POR INCLUSIÓN MOLECULAR A PARTIR DE CÁSCARA Y SEMILLA DE CAMU CAMU (Myrciaria dubia)

Camu camu (Myrciaria dubia) is a fruit from the Peruvian Amazon, highly valued for its high content of vitamin C, which is concentrated in its pulp. Due to this nutritional characteristic, it is processed into juices and extracts. However, its industrialization generates a considerable amount of waste. Therefore, its utilization is vital to reduce environmental pollution. The content of phenolic compounds in the peel and seed of camu camu has been studied, indicating that factors such as drying temperature and the method of stabilizing the concentrated powder are key to preserving its antioxidant activity. The objective of the study was to evaluate two drying temperatures (50 and 65°C) on camu camu seeds and peels, analyzing their effect on the total phenol content and the efficacy of atomization encapsulation and molecular inclusion of the concentrated extract at the optimal temperature. Extraction was conducted out with food-grade ethanol solvent at a ratio of 1:40 (g/g), at 55°C for 30 minutes, then concentrated to 60% in a rotary evaporator. At 50°C, a lower of phenolics (4979.99 ± 94.24 mg gallic acid equivalent (GAE)/100g of sample) was found in the peel and seed mixture, and total anthocyanins in the peel (47.82 ± 3.93 mg cyanidin/100 g sample).. Atomization and molecular inclusion of the concentrated extract showed efficacy in in retaining the encapsulated total phenols. In conclusion, using a temperature of 50°C for drying has a lesser impact on the content of polyphenols. Additionally, two alternatives for stabilizing the extract are presented: with maltodextrin and molecular inclusion with cyclodextrin, both equally effectives.

Microencapsulation for Pharmaceutical Applications: A Review.

In order to improve bioavailability, stability, control release, and target delivery of active pharmaceutical ingredients (APIs), as well as to mask their bitter taste, to increase their efficacy, and to minimize their side effects, a variety of microencapsulation (including nanoencapsulation, particle size <100 nm) technologies have been widely used in the pharmaceutical industry. Commonly used microencapsulation technologies are emulsion, coacervation, extrusion, spray drying, freeze-drying, molecular inclusion, microbubbles and microsponge, fluidized bed coating, supercritical fluid encapsulation, electro spinning/spray, and polymerization. In this review, APIs are categorized by their molecular complexity: small APIs (compounds with low molecular weight, like Aspirin, Ibuprofen, and Cannabidiol), medium APIs (compounds with medium molecular weight like insulin, peptides, and nucleic acids), and living microorganisms (such as probiotics, bacteria, and bacteriophages). This article provides an overview of these microencapsulation technologies including their processes, matrix, and their recent applications in microencapsulation of APIs. Furthermore, the advantages and disadvantages of these common microencapsulation technologies in terms of improving the efficacy of APIs for pharmaceutical treatments are comprehensively analyzed. The objective is to summarize the most recent progresses on microencapsulation of APIs for enhancing their bioavailability, control release, target delivery, masking their bitter taste and stability, and thus increasing their efficacy and minimizing their side effects. At the end, future perspectives on microencapsulation for pharmaceutical applications are highlighted.

Encapsulación por inclusión molecular del aceite esencial de naranja: Efecto del método de secado en las características físicas, químicas, estructurales y estabilidad

Previous investigations suggested the orange essential oil as antimicrobial and natural antioxidant; however, the high volatility and sensibility due to extern factors are imitating its applications. Thus, the encapsulation is an ideal alternative of protection for essentials oils and the molecular inclusion has greater advantages compared to others, but the drying method and temperature can influence its characteristics and stability. Therefore, the orange essential oil was microencapsulated into beta-cyclodextrin (β-CD), and was evaluated the effect of drying by stove, lyophilization and atomization (160, 180 and 200 °C) on humidity, water activity, encapsulation efficiency, yield, and stability (82% relative humidity for 36 days). The microparticles were analyzed by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The best drying method was lyophilization achieved an encapsulation efficiency of 97,35%, humidity 1,76%, water activity 0,54, and low hygroscopicity 0,20%. The results by FTIR found the formation and loss of some bonds between orange essential oil and beta-cyclodextrin, probably by effect of temperature. The lyophilized microparticles presented best stability with final efficiency of 52,53% with low humidity and water activity. This study makes it possible to establish the best drying method in cases of molecular inclusion, which may be useful in future applications when developing products.

Supramolecular "baking powder": a hexameric halogen-bonded phosphonium salt cage encapsulates and functionalises small-molecule carbonyl compounds.

We report a hexameric supramolecular cage assembled from the components of a Wittig-type phosphonium salt, held together by charge-assisted halogen bonds. The cage reliably encapsulates small polar molecules, including aldehydes and ketones, to provide host-guest systems where components are pre-formulated in a near-ideal stoichiometry for a mechanochemical base-activated Wittig olefination. These pre-formulated solids represent a proof-of-principle for a previously not reported supramolecular design of solid-state reactivity in which the host for molecular inclusion also acts as a complementary reagent for the subsequent chemical transformation of an array of guests. The host-guest solid-state complexes can act as supramolecular surrogates to their Wittig olefination vinylbromide products in a Sonogashira-type coupling that enables one-pot mechanochemical conversion of an aldehyde to an enediyne.

Cascade Bioreactors Based on Host–Guest Molecular Inclusion Complexes for Triple‐Negative Breast Cancer Therapy via Inducing Ferroptosis

AbstractTriple‐negative breast cancer (TNBC) poses significant challenges in tumor treatment. Ferroptosis, as a novel cell death mechanism, holds promise as a potential therapeutic strategy for TNBC. In this study, cascade bioreactors based on host–guest molecular inclusion complexes (PCFP@PL/p53) are constructed for TNBC therapy via inducing ferroptosis. The bioreactors are composed of hydrophobic hemirotaxane (mPEG‐β‐CD/α‐CD) and hydrophilic multi‐branched polyethyleneimine‐ferrocene (PEI‐Fc). They are linked by the reactive oxygen species (ROS)‐responsive molecular switch β‐CD@Fc, which can be activated by high levels of ROS. This activation leads to the rapid disassembly of PCFP@PL/p53 and the subsequent release of the loaded piperlongumine (PL) and p53 plasmids. In addition to acting as a “switch,” Fc can react with hydrogen peroxide (H2O2) in a Fenton reaction to produce hydroxyl radicals. PL decreases intracellular reduced glutathione and induces H2O2 accumulation, which corporates with Fc to launch ferroptosis and activated p53. The activated p53 disrupts the SLC7A11‐GSH‐GPX4 pathway, further increasing the intracellular ROS levels, resulting in a cascade amplification of ROS that ultimately induces massive ferroptosis. Meanwhile, the PCFP@PL/p53‐induced ferroptosis also activates the immune system in vivo, restricting the growth and metastasis of TNBC, thus providing a novel approach for TNBC therapy based on ferroptosis.

A Polymer-Derived Co(Fe)Ox Oxygen Evolution Catalyst Benefiting from the Oxidative Dehydrogenative Coupling of Cobalt Porphyrins.

Thin films of cobalt porphyrin conjugated polymers bearing different substituents are prepared by oxidative chemical vapor deposition (oCVD) and investigated as heterogeneous electrocatalysts for the oxygen evolution reaction (OER). Interestingly, the electrocatalytic activity originates from polymer-derived, highly transparent Co(Fe)Ox species formed under operational alkaline conditions. Structural, compositional, electrical, and electrochemical characterizations reveal that the newly formed active catalyst greatly benefited from both the polymeric conformation of the porphyrin-based thin film and the inclusion of the iron-based species originating from the oCVD reaction. High-resolution mass spectrometry analyses combined with density functional theory (DFT) calculations showed that a close relationship exists between the porphyrin substituent, the extension of the π-conjugated system cobalt porphyrin conjugated polymer, and the dynamics of the polymer conversion leading to catalytically active Co(Fe)Ox species. This work evidences the precatalytic role of cobalt porphyrin conjugated polymers and uncovers the benefit of extended π-conjugation of the molecular matrix and iron inclusion on the formation and performance of the true active catalyst.

A Comparative Study between Onion Peel Extracts, Free and Complexed with β-Cyclodextrin, as a Natural UV Filter to Cosmetic Formulations

The growing concern regarding the adverse effects of synthetic UV filters found in sunscreens has spurred significant attention due to their potential harm to aquatic ecosystems and human health. To address this, the present study aimed to extract and microencapsulate sensitive bioactive compounds derived from by-product onion peel (OP) by molecular inclusion using β-cyclodextrin as the wall material. Identification and quantification of bioactive compounds within the extract were conducted through high-performance liquid chromatography (HPLC-DAD) analysis, revealing quercetin and resveratrol as the primary constituents. The photoprotection capacity, evaluated by the sun protection factor (SPF), revealed a protection factor comparable to the value for a synthetic UV filter. The produced microparticles presented high antioxidant capacity, significant photoprotection capacity, encapsulation efficiency of 91.8%, mean diameter of 31 μm, and polydispersity of 2.09. Furthermore, to comprehensively evaluate the performance of OP extract and its potential as a natural UV filter, five O/W emulsions were produced. Results demonstrated that microparticles displayed superior ability in maintaining SPF values over a five-week period. Photoprotection evaluation–skin reactivity tests revealed that both extract and microparticles absorb UV radiation in other regions of UV radiation, revealing their potential to be used as a natural UV filter to produce a sustainable and eco-friendly value-added sunscreen.

A comprehensive study on flavor/cyclodextrin inclusion complexes

Flavors, being highly volatile compounds used in various circumstance, often require encapsulation to facilitate their handling and processing. Among different encapsulation strategies, molecular inclusion complexation with cyclodextrins through host-guest interactions is one of the most commonly employed approach. This study focuses on the fabrication of different kinds of flavor/cyclodextrin inclusion complexes and the identification of inclusion regularities, as well as the prediction of encapsulation results based on the chemical structures and oil-water partition coefficients of flavors. Meanwhile, the property characterizations of representative inclusion complexes confirm improvements in sustained release ability and flavors stability. These inclusion complexes have potential applications in the fields of food and tobacco processing. Furthermore, we successfully prepare the inclusion products with stable loading capacities and yields in a 100 L reactor, suggesting the significant potential for industrial-scaled production using the preparation method for flavor/cyclodextrin inclusion complexes outlined in this study.

Nanofibers of Glycyrrhizin/Hydroxypropyl-β-Cyclodextrin Inclusion Complex: Enhanced Solubility Profile and Anti-inflammatory Effect of Glycyrrhizin.

Despite having a wide range of therapeutic advantages, glycyrrhizin (GL) has few commercial applications due to its poor aqueous solubility. In this study, we combined the benefits of hydroxypropyl β-cyclodextrin (HP-βCD) supramolecular inclusion complexes and electrospun nanofibers to improve the solubility and therapeutic potential of GL. A molecular inclusion complex containing GL and HP-βCD was prepared by lyophilization at a 1:2 molar ratio. GL and hydroxypropyl β-cyclodextrin inclusion complexes were also incorporated into hyaluronic acid (HA) nanofibers. Prepared NF was analyzed for physical, chemical, thermal, and pharmaceutical properties. Additionally, a rat model of carrageenan-induced hind paw edema and macrophage cell lines was used to evaluate the anti-inflammatory activity of GL-HP-βCD NF. The DSC and XRD analyses clearly showed the amorphous state of GL in nanofibers. In comparison to pure GL, GL-HP-βCD NF displayed improved release (46.6 ± 2.16% in 5min) and dissolution profiles (water dissolvability ≤ 6s). Phase solubility results showed a four-fold increase in GL solubility in GL-HP-βCD NF. In vitro experiments on cell lines showed that inflammatory markers like IL-1β, TNF-α, and IL-6 were significantly lower in GL-HP-βCD NF compared to pure GL (p < 0.01 and p < 0.05). According to in vivo results, the prepared nanofiber exhibits a better anti-inflammatory effect than pure GL (63.4% inhibition vs 53.7% inhibition). The findings presented here suggested that GL-HP-βCD NF could serve as a useful strategy for improving the therapeutic effects of GL.

Inclusion Complexes of β-Cyclodextrin with Salvia officinalis Bioactive Compounds and Their Antibacterial Activities

In the present study, the formation of molecular inclusion complexes of Salvia officinalis (sage) bioactive compounds with β-cyclodextrin (β-CD) was evaluated. Sage essential oil (SEO)/β-CD inclusion complexes (ICs) were prepared by co-precipitation at iso-molecular concentrations, and Fourier transform infrared spectroscopy (FT-IR) was applied for the confirmation of the ICs’ formation. Quantification of the SEO in the inclusion complexes was performed spectrophotometrically at 273 nm using an SEO standard curve. The SEO and its inclusion complexes were evaluated for their antimicrobial activity against Escherichia coli, Staphylococcus aureus and Listeria monocytogenes. The results showed that β-CD effectively formed inclusion complexes with SEO in satisfactory yields. The antimicrobial activity of the SEO in prepared complexes with β-CD was exhibited against L. monocytogenes and S. aureus and was proportional to their concentrations but was less pronounced.

Targeted intracellular delivery of antitubercular bioactive(s) to Mtb infected macrophages via transferrin functionalized nanoliposomes

The packaging of antimicrobials/chemotherapeutics into nanoliposomes can enhance their activity while minimizing toxicity. However, their use is still limited owing to inefficient/inadequate loading strategies. Several bioactive(s) which are non ionizable, and poorly aqueous soluble cannot be easily encapsulated into aqueous core of liposomes by using conventional means. Such bioactive(s) however could be encapsulated in the liposomes by forming their water soluble molecular inclusion complex with cyclodextrins. In this study, we developed Rifampicin (RIF) − 2-hydroxylpropyl-β-cyclodextrin (HP-β-CD) molecular inclusion complex. The HP-β-CD-RIF complex interaction was assessed by using computational analysis (molecular modeling). The HP-β-CD-RIF complex and Isoniazid were co-loaded in the small unilamellar vesicles (SUVs). Further, the developed system was functionalized with transferrin, a targeting moiety. Transferrin functionalized SUVs (Tf-SUVs) could preferentially deliver their payload intracellularly in the endosomal compartment of macrophages. In in vitro study on infected Raw 264.7 macrophage cells revealed that the encapsulated bioactive(s) could eradicate the pathogen more efficiently than free bioactive(s). In vivo studies further revealed that the Tf-SUVs could accumulate and maintain intracellular bioactive(s) concentrations in macrophages. The study suggests Tf-SUVs as a promising module for targeted delivery of a drug combination with improved/optimal therapeutic index and effective clinical outcomes.

Estimation of the Controlled Release of Antioxidants from β-Cyclodextrin/Chamomile (Matricaria chamomilla L.) or Milk Thistle (Silybum marianum L.), Asteraceae, Hydrophilic Extract Complexes through the Fast and Cheap Spectrophotometric Technique.

This is the first study on the modeling of the controlled release of the estimated antioxidants (flavonoids or flavonolignans) from β-cyclodextrin (β-CD)/hydrophilic vegetable extract complexes and the modeling of transdermal pharmaceutical formulations based on these complexes using an overall estimation by the spectrophotometric method. The Korsmeyer-Peppas model was chosen for evaluating the release mechanisms. β-CD/chamomile (Matricaria chamomilla L., Asteraceae) ethanolic extract and β-CD/milk thistle (Silybum marianum L., Asteraceae) ethanolic extract complexes were obtained by the co-crystallization method with good recovering yields of 55-76%, slightly lower than for β-CD/silibinin or silymarin complexes (~87%). According to differential scanning calorimetry (DSC) and Karl Fischer water titration (KFT), the thermal stability of complexes is similar to β-CD hydrate while the hydration water content is lower, revealing the formation of molecular inclusion complexes. In the Korsmeyer-Peppas model, β-CD/M. chamomilla flower extract complexes reveal Case II transport mechanisms, while the corresponding complexes with leaf extracts indicate non-Fickian diffusion for the controlled release of antioxidants in ethanol 60 and 96%. The same non-Fickian diffusion was revealed by β-CD/S. marianum extract and β-CD/silibinin complexes. On the contrary, almost all model transdermal pharmaceutical formulations based on β-CD/M. chamomilla extract complexes and all those based on β-CD/S. marianum extract complexes revealed non-Fickian diffusion for the antioxidant release. These results indicate that H-bonding is mainly involved in the diffusion of antioxidants into a β-CD based matrix, while the controlled release of antioxidants in model formulations is mainly due to hydrophobic interactions. Results obtained in this study can be further used for studying the particular antioxidants (namely rutin or silibinin, quantified, for example, by liquid chromatographic techniques) for their transdermal transport and biological effects in innovatively designed pharmaceutical formulations that can be obtained using "green" methods and materials.

Competitive formation of molecular inclusion complexes of chlordecone and β-hexachlorocyclohexane with natural cyclodextrins: DFT and molecular dynamics study.

Chlordecone (CLD) and β-hexachlorocyclohexane (β-HCH) are chlorinated pesticides that coexist as persistent organic pollutants in the groundwater of several countries in the Caribbean, being an environmental issue. This work evaluates theoretically the competitive formation of host-guest complexes pesticides@cyclodextrines (CDs) as an alternative for water purification and selective separation of pesticides. Quantum mechanical calculations based on density functional theory (DFT) and classical molecular dynamics (MD) simulations were used to achieve information on geometries, energies, structure, and dynamics of guest-host complexes in the gas phase, implicit solvent medium, and in aqueous solutions. DFT studies showed that interactions of both pesticides with CDs are mediated by steric factors and guided by maximization of the hydrophobic interactions either with the other pesticide or with the CD cavity's inner atoms. MD results corroborate the formation of stable complexes of both pesticides with the studied CDs. α-CD exhibited a preference for the smaller β-HCH molecule over the CLD that could not perturb the formed complex. The simulation of competitive formation with γ-CD illustrated that this molecule could accommodate both pesticides inside its cavity. These results suggest that CDs with smaller cavity sizes such as α-CD could be used for selective separation of β-HCH from CLD in water bodies, while γ-CD could be used for methods that aim to remove both pesticides at the same time.

Preparation and Characterization of a Biopesticide Based on Artemisia herba-alba Essential Oil Encapsulated with Succinic Acid-Modified Beta-Cyclodextrin

Numerous essential oils have been researched as biopesticides because of their effectiveness and environmental safety. Nevertheless, encapsulation is necessary to improve its physical, chemical, and biological properties. Therefore, this paper aims to investigate the physicochemical characteristics and antifungal activity of the Artemisia herba-alba essential oil (HAEO) encapsulated in succinic acid-modified β-cyclodextrin (SACD). Hydrodistillation was used to extract a yellowish oil from the plant A. herba-alba, and gas chromatography coupled to mass spectrometry was performed to determine the chemical composition. The scanning electron microscope, Fourier transform infrared, thermogravimetric analysis, and docking studies were combined to validate the molecular inclusion of HAEO with SACD. The antifungal activity was examined against Botrytis cinerea by direct contact with a potato dextrose agar. The results showed that the main compound in HAEO was α-thujone (65.0%). Furthermore, HAEO has been successfully incorporated into SACD with a binding energy value of −5.3 kJ·mol−1, and its thermal stability improved. At a 0.1% concentration, HAEO in encapsulated form showed a higher ability to inhibit B. cinerea (38.34%), compared to EO in free form (12.00%). Thus, these findings produced evidence that the strategy of encapsulating EOs by SACD can develop novel B. cinerea inhibitors and a promising alternative biopesticide.